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Effects of polyamidoamine dendrimer on neuronal differentiation from human neural progenitor cells using the neurosphere assay

ABSTRACT: Polyamidoamine (PAMAM) dendrimers have been investigated for the development of engineered nanomaterial drug delivery systems and other industrial uses. However, the major concern for their potential adverse effects on human neural progenitor cells remains unclear. In the present study, we employed human neural progenitor cells (hNPCs) to study the effects of G4-PAMAM dendrimers on neuronal differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE65875 | GEO | 2015/02/13

SECONDARY ACCESSION(S): PRJNA275274

REPOSITORIES: GEO

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Effects of polyamidoamine dendrimer on neuronal differentiation from human neural progenitor cells using the neurosphere assay

Project description:Polyamidoamine (PAMAM) dendrimers have been investigated for the development of engineered nanomaterial drug delivery systems and other industrial uses. However, the major concern for their potential adverse effects on human neural progenitor cells remains unclear. In the present study, we employed human neural progenitor cells (hNPCs) to study the effects of G4-PAMAM dendrimers on neuronal differentiation. Neurospheres were treated with PAMAM dendrimer-NH2 (10 M-NM-<g/mL) for 72 h. Four neurospheres from the treatment and control groups were pooled together, and RNAs were isolated from each group.

2015-02-13 | E-GEOD-65875 | biostudies-arrayexpress

Gene expression changes in the retina following human neural progenitor cell injection into a rodent model for retinal degeneration

Project description:The goal of this study is to compare gene expression changes in retinal degenerate Royal College of Surgeons (RCS) rats following an injection of human neural progenitor cells (hNPCs) using RNA-seq, as compared to RCS rats receiving a sham surgery and wild-type Long Evans rats. These changes may lead to understanding of the therapeutic potential of hNPCs in inducing photoreceptor survival and visual function preservation. RNA-seq from wild-type Long Evans rats, retinal degenerate Royal College of Surgeons (RCS) rats, and RCS rats following transplantation of human neural progenitor cells (hNPCs)

2016-05-16 | E-GEOD-70600 | biostudies-arrayexpress

Expression data from +7 hNPCs and diploid hNPCs

Project description:Human Neural progenitor cells have been found to have karyotypic abnormalities. In this study we explored the gene changes between hNPCs that are karyotypically normal and hNPCs with a trisomy of chromosome 7. We used Affymetrix GeneChips to study gene expression changes between karyotypically normal hNPCs and trisomy 7 hNPCs. Cells grown in culture for ~20 passages from diploid and + 7 hNPCs were selected for RNA extraction and hybridization on Affymetrix microarrays.

2009-10-01 | E-GEOD-18349 | biostudies-arrayexpress

Expression data from +7 hNPCs and diploid hNPCs

2009-10-01 | GSE18349 | GEO

In vitro and in vivo proteomic comparison of human neural progenitor cell-induced photoreceptor survival

Project description:Retinal degenerative diseases are some of the leading causes of blindness with few treatments. Various cell-based therapies have aimed to slow the progression of vision loss by preserving light-sensing photoreceptor cells. A subretinal injection of human neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) rat model of retinal degeneration has aided in photoreceptor survival, though the mechanisms are mainly unknown. Identifying the retinal proteomic changes that occur following hNPC treatment will lead to better understanding of neuroprotection. To mimic the retinal environment following hNPC injection, a co-culture system of retinas and hNPCs was developed. Less cell death occurred in RCS retinal tissue co-cultured with hNPCs than in retinas cultured alone, suggesting that hNPCs provide retinal protection in vitro. Comparison of ex vivo and in vivo retinas identified NRF2-mediated oxidative response signaling as an hNPC-induced pathway. This is the first study to compare proteomic changes following treatment with hNPCs in both an ex vivo and in vivo environment, further allowing the use of ex vivo modeling for mechanisms of retinal preservation. Elucidation of the protein changes in the retina following hNPC treatment may lead to the discovery of mechanisms of photoreceptor survival and its therapeutic for clinical applications.

2018-12-17 | PXD011491 | Pride

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Gene expression changes in the retina following human neural progenitor cell injection into a rodent model for retinal degeneration

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Transcriptomic response of zebrafish embryos to Polyamidoamine (PAMAM) dendrimers

Project description:We are presenting here the application of toxicogenomics to perform the evaluation of toxic effects of two polyamidoamine dendrimers (Generation3 and Generation4) on the developing zebrafish embryo. They are nanomaterials of special concern under the toxicological point of view because of their relatively high solubility in water and bioavailability. Zebrafish embryo toxicity assays (zFET) showed that G3 was more toxic to zebrafish than G4, and that both compounds were several orders of magnitude more toxic than other carbonaceous nanomaterials, like carbon fullerenes or nanotubes. The results suggest a variety of MoA for different dendrimers, probably related to the nature and number of the chemical groups attached to their surface. They also confirm the relatively high bioavailability of these compounds, a key factor for the assessment of the risk associated to their use and release into the environment. About 5% genes were affected by the treatment. Gene ontology (GO) analyses show that these genes are involved in the oxidation-reduction process and also in the nervous system development. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of generations of dendrimers studied. Two different treatments were performed in this study. Zebrafish fertlized eggs were exposed to PAMAM dendrimer G3 and G4 during 48h. 3 biological replicates per studied dendrimer are included such as each control sample.

2013-11-12 | E-GEOD-41333 | biostudies-arrayexpress

Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors

Project description:DNA methylation is an important epigenetic modification that is thought to contribute to the maintenance of genomic integrity in somatic cells, in part through the silencing of transposable elements (TEs). In this study we used CRISPR/Cas9 mediated gene editing to disrupt DNMT1, the key maintenance methyltransferase in somatic human cells. Surprisingly, and in contrast to findings in mouse, inactivation of DNMT1 in human neural progenitor cells (hNPCs) resulted in viable proliferating cells that maintained the expression of appropriate marker genes. Removal of DNA methylation in hNPCs resulted in a specific activation of hominid-specific LINE-1 elements (L1s), while other classes of TEs remained silent. We also found that the transcriptionally activated L1s acted as alternative promoters for many protein-coding genes involved in neuronal functions, uncovering an L1-based transcriptional network influencing neuronal protein-coding genes. Our results prove novel mechanistic insight into the role of DNA methylation in somatic human cells.

2019-05-30 | PXD008648 | Pride

Molecular Signatures Associated with ZIKV Exposure in Human Cortical Neural Progenitors and Astrocytes

Project description:Zika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function remains elusive. Here we systematically profiled transcriptomes of human neural progenitor cells (hNPCs) and astrocytes exposed to Asian ZIKVC, African ZIKVM, and Dengue virus (DENV). DENV causes distinct gene expression changes; and ZIKV has a broader impact on the expression of gene involved in DNA replication and repair. While overall expression profiles are similar, ZIKVC, but not ZIKVM, induces upregulation of viral response genes. Upon ZIKV infection, astrocytes exhibit more prominent transcriptome changes than hNPCs, particularly enriching genes related to inflammatory response and cytokine production pathways. Our analyses reveal cell-type- and strain-specific molecular signatures associated with ZIKV infection, and identify astrocytes as a major direct target of ZIKV. Further investigation of ZIKV-host interactions based our transcriptomic datasets may help to illuminate neural virulence determinants of ZIKV in patients. Gene Expression Analyses of the cells infected with different flaviviruses

2016-08-23 | E-GEOD-80434 | biostudies-arrayexpress

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